The inhibition of malignant cell induction and proliferation is the primary goal of cancer prevention and treatment. Physiological changes that are coincident with the occurrence of cancer may indicate phenomena that are either causative or protective with regard to the development and progression of the disease and are, therefore, of significant interest to clinical researchers.
Eosinophils are granulocytic leukocytes with bi-lobed nuclei, named for their property of staining red in eosin dye. Their production from bone marrow stem cells, maturation and activation occur specifically in response to signals mediated by interleukin-5 (Weller, 1991, New England J. Med, 324: 1110-1118). These cells reside largely in epithelium-lined tissues that are in contact with the environment, such as the gastrointestinal- and lower genitourinary tracts, as well as the respiratory epithelium (Devos et al., 1995, J. Leuk. Biol., 57: 813-819; Weller, 1991, supra; Wong et al., 1990, J. Exp. Med., 172: 673-681).
Tissue eosinophilia in malignancies of epithelial origin has been reported since 1893 (Reinback, 1893, Arch. Klin. Chir., 46: 486-562); however, the role of the eosinophil in the cancer etiology remains unclear. Eosinophil influx has been shown to be associated with a number of human tumors, primarily carcinomas (Goldsmith et al., 1987, Otolaryngology-Head and Neck Surgery, 96: 319-|-324; Iwasaki et al., 1986, Cancer, 58: 1321-1327; Kolb and Muller, 1979, Br. J. Cancer, 40: 410-416; Lowe and Fletcher, 1984, Histopathology, 8: 627-632; Loew et al., 1984, Histopathology, 8: 619-625; McGinnis et al., 1989, Cancer Res., 49: 5989-5993; Pretlow et al., 1983, Cancer Res., 43: 2997-3000).
While eosinophils have been found not to suppress growth in interleukin-5 transfected tumor cells (Kuger-Krasagakes et al., 1993, Eur. J. Immunol., 23: 992-995), suppression of tumor development has been demonstrated in cells transfected with genes encoding either IL-4 (Tepper et al., 1989, Cell, 57: 503-512) or monocyte chemoattractant MCP-1/JE (Rollins and Sunday, 1991, Mol. Cell. Biol., 11: 3125-3131) through a host-reactive inflammatory response that consists of significant tissue eosinophilia. Using antibodies that specifically block the accumulation of granulocytes at the site of inflammation, it further has been demonstrated that eosinophils are directly involved in the observed IL-4-mediated tumor cytotoxicity (Tepper et al., 1992, Science, 257: 548-551).
Published clinical evidence supports both host-protective and tumor-inducing roles for eosinophils in cancer, thereby providing little or no therapeutic guidance. Stromal eosinophilia has been suggested as a favorable prognostic indicator in cases of human neoplasms, including head and neck cancers (Goldsmith et al., 1987, supra), which supports the hypothesis of a "protective" role of eosinophils in cancer. Increased survival and decreased metastasis correlate positively with the level of tumor associated tissue eosinophilia (TATE) in patients suffering colonic carcinoma (Pretlow et al., 1983, supra) and tumors of the uterine cervix (Kapp and Livolsi, 1983, Gynecologic Oncology, 16: 19-30). Heavy eosinophilic infiltration has been suggested as indicating an unfavorable prognosis in well-differentiated squamous cell carcinomas of the oral cavity (Horiuchi et al., 1993, J. Surg. Oncol., 53: 92-96); however, this finding is contradicted by reports that massive tissue eosinophilia is associated with a favorable prognosis in cases of squamous cell carcinoma of the oral cavity, external genitalia, and anus (Lowe and Fletcher, 1984, Histopathology, 8: 627-632) as well as tumors of the bladder (Lowe and Fletcher, 1984, J. Clin. Pathol., 37: 500-502). It has also been reported that interleukin-4 transfected tumor cells lose their ability to form tumors if eosinophils are present (Tepper et al., 1989, Cell, 57: 503-512).
There is a need in the art for improved methods for the prevention and treatment of cancer.